scholarly journals Deletion of the yeast homologue of the human gene associated with Friedreich's ataxia elicits iron accumulation in mitochondria

FEBS Letters ◽  
1997 ◽  
Vol 411 (2-3) ◽  
pp. 373-377 ◽  
Author(s):  
Françoise Foury ◽  
Ornella Cazzalini
Keyword(s):  
Human Gene ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Iron Accumulation

scholarly journals Complex I and ATP Content Deficiency in Lymphocytes from Friedreich's Ataxia

2009 ◽  
Vol 36 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Mohammad Mehdi Heidari ◽  
Massoud Houshmand ◽  
Saman Hosseinkhani ◽  
Shahriar Nafissi ◽  
Mehri Khatami
Keyword(s):  
Respiratory Chain ◽  
Complex I ◽  
Age Of Onset ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Iron Accumulation ◽  
Atp Content ◽  
Respiratory Chain Complexes ◽  
Intracellular Atp ◽  
Complex I Activity

Background:Friedreich's ataxia (FRDA) is an inherited recessive disorder characterized by progressive neurological disability and heart abnormalities. A deficiency in the protein frataxin causes this disease. Frataxin deficiency leads to progressive iron accumulation in mitochondria, excessive free radical production and dysfunction of respiratory chain complexes. The expansion (GAA) repeat in the first intron causes decreased frataxin expression by interfering with transcription.Methods:Activity of mitochondrial respiratory chain complex I (measured as NADH ferricyanide reductase) and intracellular ATP measurement was performed on lymphocyte of FRDA patients (n=12) and control subjects (n=25).Results:Our findings showed that complex I activity and intracellular ATP were significantly reduced (P=0.001) in patients compared with controls and we found strong correlation between complex I activity and intracellular ATP content in FRDA patients (r = 0.93; P<0.002). 8.6 and 9.0 kb deletion in mtDNA was detected in 9 patients out of 12 (75%) by multiplex polymerase chain reaction (PCR) and Southern blot analysis.Conclusions:This study suggested that a biochemical defect in complex I activity and ATP production, which may be due to iron accumulation in mitochondria, can be involved in age of onset of FRDA.

Otoneurological Findings in Friedreich's Ataxia and Other Inherited Neuropathies

1986 ◽  
Vol 25 (2) ◽  
pp. 84-91 ◽  
Author(s):  
E. Cassandro ◽  
F. Mosca ◽  
L. Sequino ◽  
F. A. De Falco ◽  
G. Campanella
Keyword(s):  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Inherited Neuropathies

scholarly journals Echocardiographic Findings in Friedreich's Ataxia

1976 ◽  
Vol 3 (4) ◽  
pp. 329-332 ◽  
Author(s):  
H.F. Gattiker ◽  
A. Davignon ◽  
A. Bozio ◽  
J. Batlle-Diaz ◽  
G. Geoffroy ◽  
...  
Keyword(s):  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
Ventricular Free Wall ◽  
Slight Reduction ◽  
Free Wall ◽  
Left Ventricular Free Wall ◽  
Echocardiographic Examination ◽  
Septal Hypertrophy ◽  
Echocardiographic Findings

SUMMARY:Echocardiographic examination of 21 patients with Friedreich's ataxia (age 7 to 28 years) showed cardiac abnormalities in 90% of the cases. They were characterized by varying degrees of septal hypertrophy in 81%, left ventricular free wall hypertrophy in 61%, and a slight reduction of left ventricular internal dimension in 57% of the cases. Asymmetric septal hypertrophy (ASH) with a septal/left ventricular free wall ratio of over 1.3 was found in 29% of the cases, and systolic anterior motion (SAM) of the mitral valve in three patients. Two other patients showed evidence of a different type of cardiomyopathy with marked symmetric left ventricular hypertrophy and marked left ventricular enlargement.

Square Wave Jerks in Friedreich's Ataxia

1978 ◽  
Vol 85 (3) ◽  
pp. 400-406 ◽  
Author(s):  
Robert T. Dale ◽  
Albert W. Kirby ◽  
Robert S. Jampel
Keyword(s):  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Square Wave

scholarly journals Future Prospects of Gene Therapy for Friedreich’s Ataxia

2021 ◽  
Vol 22 (4) ◽  
pp. 1815 ◽  
Author(s):  
Gabriel Ocana-Santero ◽  
Javier Díaz-Nido ◽  
Saúl Herranz-Martín
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Autosomal Recessive ◽  
State Of The Art ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
First Intron ◽  
Progressive Neurodegeneration ◽  
Feasible Solutions ◽  
Neurogenetic Disease

Friedreich’s ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich’s ataxia. A plausible therapeutic approach is gene therapy. Indeed, Friedreich’s ataxia mouse models have been treated with viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, gene therapy is increasingly consolidating as one of the most promising therapies. However, several hurdles have to be overcome, including immunotoxicity and pheno-toxicity. We review the state of the art of gene therapy in Friedreich’s ataxia, addressing the main challenges and the most feasible solutions for them.

Sign in / Sign up

Export Citation Format

Share Document